Yu Fang-Fang, Zuo Juan, Wang Miao, Yu Shui-Yuan, Luo Kang-Ting, Sha Tong-Tong, Li Qian, Dong Zai-Chao, Zhou Guo-Yu, Zhang Feng, Guo Xiong, Ba Yue, Wang Yan-Jie
Department of Environmental Health, School of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, PR China.
Department of Environmental Health, School of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, PR China; Department of Medical Technology, Zhengzhou Shuqing Medical College, Zhengzhou, Henan 450064, PR China.
Ecotoxicol Environ Saf. 2025 Jan 15;290:117569. doi: 10.1016/j.ecoenv.2024.117569. Epub 2024 Dec 18.
T-2 toxin can induce bone and cartilage development disorder, and oxidative stress plays an important role in it. It is well known that selenomethionine (Se-Met) has antioxidative stress properties and promotes the repair of cartilage lesion, but it remains unclear whether Se-Met can relieve damaged cartilage exposure to T-2 toxin. Here, the oxidative stress and ferroptosis of chondrocytes exposure to T-2 toxin were observed. Mechanistically, T-2 toxin increased ROS, lipid ROS, MDA and Fe contents in chondrocytes, decreased GSH and GPX4 activity, and inhibited the system Xc/GSH/GPX4 antioxidant axis. In addition, the mitochondria of chondrocytes shrunk and the mitochondrial crest decreased or disappeared. However, Fer-1 (Ferrostatin-1) inhibited ferroptosis induced by T-2 toxin in chondrocytes. The Se-Met alleviated lipid peroxidation, oxidative stress, and damaged mitochondrial in T-2 toxin-infected chondrocytes, enhanced antioxidant enzyme activity, and activated the system Xc/GSH/GPX4 axis, thereby antagonizing ferroptosis of chondrocytes and alleviating articular cartilage damage. In conclusion, our findings highlight the essentiality of ferroptosis in chondrocyte caused by T-2 toxin, elucidate how Se-Met offers protection against this injury and provide research evidence for the drug treatment target of Kashin-Beck disease.
T-2毒素可诱导骨骼和软骨发育障碍，氧化应激在其中起重要作用。众所周知，硒代蛋氨酸（Se-Met）具有抗氧化应激特性并促进软骨损伤修复，但Se-Met是否能缓解受损软骨暴露于T-2毒素的情况仍不清楚。在此，观察了暴露于T-2毒素的软骨细胞的氧化应激和铁死亡。机制上，T-2毒素增加了软骨细胞中的活性氧（ROS）、脂质ROS、丙二醛（MDA）和铁含量，降低了谷胱甘肽（GSH）和谷胱甘肽过氧化物酶4（GPX4）活性，并抑制了系统Xc/GSH/GPX4抗氧化轴。此外，软骨细胞的线粒体萎缩，线粒体嵴减少或消失。然而，铁抑素-1（Fer-1）抑制了T-2毒素诱导的软骨细胞铁死亡。Se-Met减轻了T-2毒素感染的软骨细胞中的脂质过氧化、氧化应激和线粒体损伤，增强了抗氧化酶活性，并激活了系统Xc/GSH/GPX4轴，从而拮抗软骨细胞的铁死亡并减轻关节软骨损伤。总之，我们的研究结果突出了T-2毒素引起的软骨细胞铁死亡的重要性，阐明了Se-Met如何提供针对这种损伤的保护，并为大骨节病的药物治疗靶点提供了研究证据。
